The present disclosure predominantly describes use of convertible plungers according to the present invention in connection with prefilled syringes. However, a skilled artisan would readily appreciate that the invention is not limited to prefilled syringes, but may include other drug delivery devices, such as (prefilled, filled before use, or empty) syringes, cartridges and auto-injectors as well as prefilled syringes or other barrels used for diagnostics applications.
Prefilled parenteral containers, such as syringes or cartridges, are commonly prepared and sold so that the syringe does not need to be filled by the patient or caregiver before use. The syringe, and more specifically the barrel of the syringe, may be prefilled with a variety of different injection products, including, for example, saline solution, a dye for injection, or a pharmaceutically active preparation, among other items.
Prefilled parenteral containers are typically sealed with a rubber plunger, which provides closure integrity over the shelf life of the container's contents. To use the prefilled syringe, the packaging and cap are removed, optionally a hypodermic needle or another delivery conduit is attached to the distal end of the barrel, the delivery conduit or syringe is moved to a use position (such as by inserting it into a patient's tissue or into apparatus to be rinsed with the contents of the syringe), and the plunger is advanced in the barrel to inject contents of the barrel to the point of application.
Seals provided by rubber plungers in the barrel typically involve the rubber of the plunger being pressed against the barrel. Typically the rubber plunger is larger in diameter than the internal diameter of the barrel. Thus, to displace the rubber plunger when the injection product is to be dispensed from the syringe requires overcoming this pressing force of the rubber plunger. Moreover, not only does this pressing force provided by the rubber seal typically need to be overcome when initially moving the plunger, but this force also needs to continue to be overcome as the rubber plunger is displaced along the barrel during the dispensing of the injection product. The need for relatively elevated forces to advance the plunger in the syringe may increase the user's difficulty in administering the injection product from the syringe. This is particularly problematic for auto injection systems where the syringe is placed into the auto injection device and the plunger is advanced by a fixed spring. Accordingly, primary considerations concerning the use of a plunger in a prefilled parenteral container include: (1) container closure integrity (“CCI”, defined below) and gas-tightness; and (2) plunger force (defined below) required to dispense syringe contents.
In practice, maintaining CCI/gas-tightness and providing desirable plunger force tend to be competing considerations. In other words, absent other factors, the tighter the fit between the plunger and the interior surface of the container to maintain adequate CCI/gas-tightness, the greater the force necessary to advance the plunger in use. In the field of medical syringes, it is important to ensure that the plunger can move at a substantially constant speed and with a substantially constant and relatively low force when advanced in the barrel. In addition, the force necessary to initiate plunger movement and then continue advancement of the plunger should be low enough to enable comfortable administration by a user and prevent jolting or unnecessarily high pressing force that can cause patient discomfort.
Plunger force is essentially a function of the coefficients of friction of each of the contacting surfaces (i.e., the plunger surface and interior syringe wall surface) and the normal force exerted by the plunger against the interior wall of the syringe. The greater the respective coefficients of friction and the greater the normal force, the more force required to advance the plunger. Accordingly, efforts to improve plunger force should be directed to reducing friction and lowering normal force between contacting surfaces. However, such efforts are preferably tempered by the need to maintain adequate CCI and gas-tightness, as discussed above.
To reduce friction and thus improve plunger force, lubrication is traditionally applied to the barrel-contacting engagement surface of the plunger, the interior surface of the barrel, or both. Liquid or gel-like flowable lubricants, such as free silicone oil (e.g., polydimethylsiloxane or “PDMS”), may provide a desired level of lubrication between the plunger and the barrel to optimize plunger force. PDMS is, in fact, a standard flowable lubricant used in the industry. However, for preferred embodiments of the invention, use of flowable lubricant between the plunger and the barrel is not desired. One reason is that a flowable lubricant can mix and interact with the drug product in a syringe, potentially degrading the drug or otherwise affecting its efficacy and/or safety. Degradation is particularly an issue in the case of protein compositions and polypeptide compositions, which occupy a market with tremendous growth potential. Further, such lubricants may in some cases be problematic if they are injected into the patient along with the drug product. In addition, flowable lubricants, when used with prefilled syringes, may migrate away from the plunger over time, resulting in spots between the plunger and the interior surface of the container with little or no lubrication. This may cause a phenomenon known as “sticktion,” an industry term for the adhesion between the plunger and the barrel that needs to be overcome to break out the plunger and allow it to begin moving. For these reasons, there is an industry need for an “oil free” solution, i.e., a plunger that is entirely or at least substantially free of flowable lubricant between the plunger and the barrel and wherein such flowable lubricant is absent from the drug product stream.
As an alternative (or in addition) to flowable lubricants, plungers may be made from materials having lubricious properties or include friction-reducing coatings or film laminates on their exterior surfaces. Examples of such plungers include, for example: the i-COATING by TERUMO, which is disclosed in Canadian Patent No. 1,324,545, incorporated by reference herein in its entirety; W.L. Gore extended ETFE film on a rubber plunger; and the CZ plunger by WEST. However, film coated plungers alone are considered to provide inadequate CCI or gas-barrier properties. For example, while fluoropolymer films on plungers provide excellent lubricious properties, they are known to provide poor gas barriers. Accordingly, a conventional fluropolymer film laminated plunger alone may not be a viable solution for a prefilled syringe that houses product which is sensitive to certain gases.
Thus, there is a need for plungers that balance desirable plunger force in a parenteral container with maintaining adequate CCI and (as the case may be) gas-tight sealing to prevent drug leakage, protect the drug product and attain sufficient product shelf life. In addition, there is a need to provide adequate lubricity to achieve a desired plunger force while preventing adverse effects of flowable lubricant-generated particles and interaction with the drug product held by the container. There is a further need to optimize these factors while reducing manufacturing costs and complexity. The subject invention preferably addresses those needs, and others.